TGM1 Gene - Transglutaminase 1
Key Enzyme in Epidermal Barrier Formation and Ichthyosis Pathogenesis
Gene Information Card
| Symbol | TGM1 |
|---|---|
| Full Name | Transglutaminase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q12 |
| NCBI Gene ID | 7051 ncbi.nlm.nih.gov/gene/7051 |
| Ensembl ID | ENSG00000162493 |
| UniProt ID | P22735 |
| OMIM ID | 190195 |
| HGNC ID | 11777 |
| Aliases | TGASE, TGase 1, TGK, KTG, TGase-1, transglutaminase K |
Description
The TGM1 gene encodes transglutaminase 1, a membrane-bound enzyme that catalyzes the cross-linking of proteins such as loricrin, involucrin, and small proline-rich proteins to form the cornified cell envelope, essential for epidermal barrier integrity. Mutations in TGM1 cause autosomal recessive congenital ichthyosis, most commonly lamellar ichthyosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lamellar ichthyosis (LI) | Loss-of-function mutations in TGM1 prevent proper cross-linking of cornified envelope proteins, leading to defective epidermal barrier and hyperkeratosis. | ClinVar, OMIM |
| Congenital ichthyosiform erythroderma (CIE) | Milder TGM1 mutations reduce but do not abolish transglutaminase activity, resulting in erythroderma and fine scaling. | ClinVar, OMIM |
| Self-healing collodion baby | Specific TGM1 missense mutations allow partial enzyme activity, leading to transient collodion membrane that resolves. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 58.6 | High |
| Esophagus | 12.3 | Medium |
| Oral mucosa | 8.9 | Medium |
| Vagina | 6.4 | Low |
| Cervix | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Keratinocytes (primary) | 72.1 | Highest expression in differentiated keratinocytes |
| HaCaT | 45.3 | Immortalized keratinocyte line |
| A431 | 22.8 | Epidermoid carcinoma cell line |
| NHEK | 68.9 | Normal human epidermal keratinocytes |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.877-2A>G | Splice site | Common in European populations | Loss of function; exon skipping leads to truncated protein |
| p.Arg142His | Missense | Found in LI patients | Reduced enzyme activity |
| p.Arg315Cys | Missense | Reported in CIE | Partial loss of function |
| c.1223_1227del | Frameshift | Rare | Premature termination, complete loss of activity |
Mutation functional classification
Loss of Function (LOF)
Most TGM1 mutations are loss-of-function, leading to autosomal recessive congenital ichthyosis (ARCI) due to defective cornified envelope formation.
Gain of Function (GOF)
No gain-of-function mutations reported for TGM1.
Dominant Negative (DN)
No dominant-negative effects described; TGM1 disease is strictly recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cornified envelope formation (Reactome: R-HSA-6809371)
• Keratinization (Reactome: R-HSA-6805567)
• Formation of the cornified envelope (KEGG: hsa04974)
Protein Summary
Transglutaminase 1 (TGase 1) is a 90 kDa membrane-anchored enzyme expressed primarily in stratified squamous epithelia. It cross-links structural proteins via epsilon-(gamma-glutamyl)lysine isopeptide bonds, forming an insoluble cornified envelope beneath the plasma membrane of terminally differentiated keratinocytes. The enzyme requires calcium for activity and is activated by proteolytic cleavage. Deficiency leads to severe skin barrier defects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TGM1 Knockout HEK293 Cell Line | EDJ-KQ2725 | Human | 7051 | Details Get a Quote |
| TGM1 Knockout HCT 116 Cell Line | EDJ-KQ22208 | Human | 7051 | Details Get a Quote |
| TGM1 Knockout HeLa Cell Line | EDJ-KQ23583 | Human | 7051 | Details Get a Quote |
| TGM1 Knockout A-549 Cell Line | EDJ-KQ63131 | Human | 7051 | Details Get a Quote |
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